J6

Ettbgu

v

g

t

M

S

m

v

D

(

e

©

0

d

CURRENT THERAPY

Oral Maxillofac Surg4:1664-1668, 2006

A Systematic Review of ProphylacticAntibiotics in the Surgical Treatment of

Maxillofacial FracturesJens O. Andreasen, DDS, Odont Drhc,* Simon S. Jensen, DDS,†

Ole Schwartz, DDS, LDS,‡ and Yören Hillerup, DDS, Dr Odont§

Purpose: A systematic review was performed to find evidence for prophylactic administration ofantibiotics in relation to treatment of maxillofacial fractures.

Methods: Four studies were retrieved that fulfilled most of the requirements of being randomizedcontrolled clinical trials.

Results: An analysis of these studies showed a 3-fold decrease in the infection rate of mandibularfractures in the antibiotic treated groups compared with the control groups. A variety of antibiotics hadbeen used with an apparently uniform effect. A “1-shot” regimen or a 1-day treatment course had a similaror perhaps even better effect than 7 days of treatment. No infections were related to condylar, maxillary,or zygoma fractures.

Conclusion: A 1-shot or 1-day administration of prophylactic antibiotics seem to be the best docu-mented to reduce infections in the management of mandibular fractures not involving the condylarregion.© 2006 American Association of Oral and Maxillofacial Surgeons

J Oral Maxillofac Surg 64:1664-1668, 2006

hoiopphTsbt

otp

ictaostt

vidence-based treatment strategies depend on applica-ion of the best knowledge a discipline can offer. Sys-ematic reviews should aim at extracting the currentest evidence within a well-defined area, and therebyive the clinician an intended unbiased tool in keepingp with an exponentially growing knowledge base.

*Consultant, Department of Oral and Maxillofacial Surgery, Uni-

ersity Hospital (Rigshospitalet), Copenhagen, Denmark.

†Assistant Professor, Department of Oral and Maxillofacial Sur-

ery, University Hospital (Glostrup), Copenhagen, Denmark; and

he Department of Oral Surgery and Stomatology, School of Dental

edicine, University of Berne, Switzerland.

‡Department Chairman, Department of Oral and Maxillofacial

urgery, University Hospital (Rigshospitalet), Copenhagen, Den-

ark.

§Professor, Department of Oral and Maxillofacial Surgery, Uni-

ersity Hospital (Rigshospitalet), Copenhagen, Denmark.

Address correspondence and reprint requests to Dr Andreasen:

epartment of Oral and Maxillofacial Surgery, University Hospital

Rigshospitalet), Blegdamsvej 9, DK-2100 Copenhagen, Denmark;

-mail: RH11323@RH.dk

2006 American Association of Oral and Maxillofacial Surgeons

278-2391/06/6411-0014$32.00/0

ooi:10.1016/j.joms.2006.02.032

1664

For many years, prophylactic antibiotic treatmentas been considered a must in the surgical treatmentf jaw fractures.1 The evidence for this preventive

ntervention, however, has been weak in a series ofther surgical disciplines.2-5 For many indications,rophylactic antibiotics have been shown to have noositive and sometimes even a negative effect (ie, aigher infection rate in antibiotic treated situations).6

he latter event being explained by the fact that noingle antibiotic can eliminate all kinds of invadingacteria and thereby may give an advantage to oppor-unistic infection.7

Several factors with a known impact on the incidencef infections in relation to maxillofacial trauma must beaken into consideration before the specific role of arophylactic antibiotic regimen can be evaluated.Two different situations exist in relation to the

nvasion of bacterias into the fracture site, namely alosed fracture (eg, mandibular condyle or ramus frac-ures and maxillary Le Fort I–III fractures) on 1 sidend open fractures with direct communication to theral cavity and/or the skin surface on the other. Notudy has so far evaluated the actual invasion of bac-eria in a healing fracture site; but the importance ofhis differentiation is apparent by the fact that healing

f fractures located in the condylar region is never

fqg

cfehci

ttsstt

nttithi

aliiott

ttdot

ts

M

swfisle

w

icctetir

RPADOS

A axillof

ANDREASEN ET AL 1665

ollowed by infection compared with the more fre-uent occurrence of infections in the mandibular an-le, body, and symphysis regions.8

Another factor to be analyzed is the treatment pro-edure used (ie, open versus closed reduction of theracture). From a previous analysis, it became appar-nt that an open procedure may lead to a 4-foldigher rate of infection.9 The type of treatment pro-edure (open or closed) should therefore also bencluded in an analysis of the effect of antibiotics.

Mandibular fractures are more prone to infectionhan maxillary fractures8; and within the mandible,he location of the fracture in the dental arch alsoeems to be of importance with the third molar regionhowing the highest frequency of infections.8 Thus,he topography of the jaw fractures is another factoro be considered.

Concerning the administration of antibiotics, aumber of factors have to be taken into account. First,he type of antibiotics administered; the dose, dura-ion, and route of administration, and finally the tim-ng of administration in relation to injury and surgicalreatment. All of these factors have been shown toave significant influence on the chance of avoiding

nfection.5

The term prophylaxis implies preventive use ofntibiotics. In the present review, antibiotic prophy-axis is interpreted as given, when no clinical signs ofnfection are present at the time of surgery, althought may be argued that any fracture open to the skin orral cavity should be considered contaminated, andhat antibiotics thereby are indicated as a part ofreatment rather than prophylactic.

Finally, an analysis of the literature should concen-rate on randomized studies, and in this regard whetherhe studies meet the requirements for a reliable studyesign, proper randomization, limited number of drop-uts, sufficient number of patients included, and utiliza-ion of relevant statistical methods.10

It was the purpose of the present systematic reviewo evaluate available randomized clinical trials to an-

Table 1. SURVEY OF STUDIES INCLUDED

Zallen andCurry,12 1975

Aderhal,13

andomization � �atient blinded to treatment � �ssessor blinded to treatment � �rop-outs accounted for � �utcome measures clearly defined � �

tatistical method � �

*Claimed, but the method is not provided.

ndreasen et al. Antibiotics for Maxillofacial Fractures. J Oral M

wer the following questions: a

1) Does antibiotic prophylaxis decrease the inci-dence of post-trauma infections in jaw fracturetreatment?

2) Are there situations where an antibiotic prophy-laxis is not indicated?

3) Which antibiotic is the drug of choice? In whatdose? And for how long?

aterial and Methods

ANALYSIS OF THE LITERATURE

The databases MEDLINE and Cochrane wereearched for relevant studies, using the following keyords: jaw fractures, mandibular fractures, maxillary

ractures, antibiotic treatment, infection, and random-zed studies. This search was supplemented by a handearch of relevant German journals not electronicallyisted and by a review of reference lists of potentiallyligible studies.For each retrieved study, the following questionsere asked (Table 1):

1) Were the patients randomly allocated to thetreatment groups?

2) Were the patients blind to treatment allocation?3) Were the treatment outcomes assessed blind?4) Were all dropouts to follow-up accounted for?5) Were the clinical outcome variables clearly de-

fined?6) Were details given of the statistical evaluation

method?

Based on this, each individual study was character-zed as a randomized controlled trial or a controlledlinical trial. To meet the criteria of a randomizedontrolled trial, the study should involve at least 1 testreatment and 1 control treatment and concurrentnrollment and follow-up of the test- and control-reated groups, in which the treatments to be admin-stered are selected by a random process such as aandom number table. Studies where the patients are

Gerlach andPape,14 1988

Chole andYee,8 1987

Heit et al,15

1997Abubaker etal,16 2001

�* � �* �*� � ? �� � � �� � � �� � � �� � � �

ac Surg 2006.

old et1983

*

ppointed to the different treatment groups using

qcw

R

cicpasmcHes

ld1copsTeddtt

etcsccastrsnsbtrma

cpoi

ltpuss7r1o

fioettctrwa

d

emapmIigcahp.otw

cscgspwermuap

1666 ANTIBIOTICS FOR MAXILLOFACIAL FRACTURES

uasi- or pseudo-randomization techniques such asoin flips, social security numbers, or days of theeek, are considered controlled clinical trials.11

esults

Four randomized studies8,12-14 were retrieved con-erning the possible benefit of prophylactic antibiot-cs in the treatment of maxillofacial fractures. Twolinical randomized studies were found that com-ared different antibiotic regimens without including

control group.15,16 A critical analysis of thesehowed that none of them fulfilled all the require-ents for a randomized controlled trial. The short-

omings of the studies are presented in Table 1.owever, as these studies represent the best knowl-dge available at the present time, the results areummarized below.

The first randomized study on the effect of prophy-actic antibiotics in the treatment of compound man-ibular fractures was published by Zallen and Curry in975.12 The material consisted of 32 patients withompound mandibular fractures who received antibi-tics (a wide variety of different antibiotics), and 30atients treated without antibiotics. A control of thetratification was made and shown to be effective.he administration of antibiotics was in 20 cases par-nterally and in 10 cases orally. A highly significantifference in complication rates was found as 6%eveloped infection complications in the antibiotic-reated group, whereas 53% developed infection inhe nontreated group (P � .0001) (Table 2).

In 1983, Aderhold et al13 published a study on theffect of antibiotic treatment of 120 mandibular frac-ures. All fractures had communication to the oralavity and were treated with miniplate osteosynthe-is. Forty cases were treated without antibiotics, 40ases with antibiotic coverage up to 48 hours, and 40ases with treatment for more than 48 hours. Typend dosage of the prescribed antibiotics are not pre-ented. Proper stratification was checked and foundo be reliable, and the numbers of open and closedeductions in the 2 groups are comparable. An almostignificantly higher infection rate was found in theontreated group (20%), whereas cases treated withhort-term antibiotics showed a frequency of 5% andeyond 48 hours of 10% (n � .06). It was concludedhat short-term antibiotic prophylaxis was effective ineducing infection; furthermore, that long-term treat-ent did not significantly reduce the risk of infections

s compared with the control group (Table 2).In 1987, Chole and Yee8 reported a prospective

linical trial of 101 patients with facial fractures. Theatients were randomly assigned to either no antibi-tic treatment or a short-term prophylaxis with an

ntravenous administration of cefazolin 1 g (a cepha- d

osporin) 1 hour before surgery and 8 hours after. Aotal of 150 fractures were diagnosed in the 101atients (6 maxillary, 24 zygomatic, and 120 mandib-lar fractures). None of the maxillary, zygomatic, andubcondylar mandibular fractures got infected, irre-pective of antibiotic prophylaxis given or not. In the9 patients with mandibular fractures, the 37 whoeceived antibiotics experienced an infection rate of4%, whereas 42 patients in the control group devel-ped infections in 43% (P � .01) of the cases.In a separate nonrandomized analysis, it was con-

rmed whether the infection rate in relation to closed orpen reduction of the mandibular fractures was influ-nced by the administration of antibiotics. It turned outhat antibiotic prophylaxis had virtually no influence onhe infection rate when the fractures were treated withlosed reduction (23% infections with administered an-ibiotics/28% infections with no antibiotics). In the openeduction group, however, 62% developed infectionshen no antibiotics were used compared with 8% in the

ntibiotic group (Table 2).It was concluded that antibiotic prophylaxis is in-

icated for mandibular fractures.In 1988, Gerlach and Pape14 examined the influ-

nce of antibiotic treatment on infection rates in 200andibular fractures all treated with open reduction

nd miniplate osteosynthesis through an intraoral ap-roach. In group I (n � 50), a 1-day antibiotic treat-ent was given, starting immediately before surgery.

n group II (n � 50), a 1-shot prophylaxis of antibiot-cs was administered immediately before surgery. Inroup III (n � 51), a 3-day course was used. Finally, aontrol group (n � 49) received no prophylacticntibiotics. The control group showed a significantlyigher infection rate (22%) compared with the 3 pro-hylactic groups (2%, 6%, and 8%, respectively) (P �

001). It was concluded that a “1-shot administration”f antibiotics in relation to intraoral osteosynthesis inhe mandible is sufficient to protect the patient fromound infection (Table 2).Two different antibiotic prophylactic regimens were

ompared in a prospective and nonrandomized clinicaltudy by Heit et al15 in 1997. A total of 90 patients withompound mandibular fractures were divided into 2roups of 45 patients. In group I, the prophylaxis con-isted of ceftriaxone (a cephalosporin) 1 g daily pre- anderioperatively until the intravenously administrationas discontinued and thereafter penicillin VK 500 mg

very sixth hour orally 1 week postoperatively. Group IIeceived an intravenous administration of penicillin G 2illion U every fourth hour pre- and perioperatively

ntil the intravenously administration was discontinuednd thereafter the same orally administered doses ofenicillin VK as for group I. Two patients in each group

eveloped an infection and thus there could not be a

di

rtm(abbw

D

ewbr

iccrahitctf

jtsa

sbm

ewbvfi

tpitt

fandm

tccpci

Z

A

G

C

A axillof

ANDREASEN ET AL 1667

emonstrated significant difference between the 2 reg-mens.

Abubaker and Rollert16 reported in 2001 preliminaryesults of a comparative, double-blind, placebo-con-rolled study of a 1-day prophylaxis versus a 5-day treat-ent with penicillin. In a limited number of patients

n � 30), no benefit of a prolonged administration ofntibiotics could be seen. However, the results shoulde interpreted with caution because of the small num-er of patients and that both open and closed reductionsere mixed in the material.

iscussion

In maxillofacial fracture treatment a multitude ofxternal sources exist for contamination of theound. In this aspect the fracture can, in most cases,e considered contaminated, implying an elevatedisk of infection.17

From this perusal of the literature, it appears stronglyndicated to use a short-term antibiotic coverage to de-rease the infection rate in relation to the treatment ofompound mandibular fractures. Approximately a 4-foldeduction in the number of infections was found. It islso of interest to observe that open reduction wasighly influenced by the use of antibiotics. This seems to

ndicate that the cause of infection could be related tohe surgical approach itself, namely damaging the prin-ipal blood supply to perform an osteosynthesis andhereby additionally exposing an injured area to bacteriarom the oral cavity or external environment.

An interesting analogue to the surgical treatment ofaw fractures appears in orthognathic surgery wherehe infection rate is normally very low, and in 3tudies has been shown not to be related to the

Table 2. COMPARISON OF POSTOPERATIVE INFECTION

Study Administration

Control

No Antib

No. x

allen and Curry,12

1975 30 16

derhold et al,13 Control 40 81983 �48hours

�48hours

erlach and Pape,14 Control 49 111988 1 day

1 shot3 days

hole and Yee,8

1987 42 18

Abbreviation: x, Number of infections.

ndreasen et al. Antibiotics for Maxillofacial Fractures. J Oral M

dministration of antibiotics.18-20 Only 1 study has r

hown a positive effect on infection rates.21 It mighte expected that the same exposure to all bacteriaay occur in orthognathic surgery.However, in jaw fracture treatment a multitude of

xternal sources exist for contamination of theound. In this aspect the fracture can, in most cases,e considered contaminated,17 with the known ele-ation in infection risk and that was also the generalnding in this survey.However, the difference might be that the injured

issue had a short exposure to oral bacteria in com-arison to jaw fractures where bacteria might have

nvaded the tissues for days (although it was shownhat the time delay until treatment did not influencehe infection rate).8

Combining the evidence from all 4 studies, theollowing can be concluded about infection rates: Itppears that there is a significant reduction in theumber of post injury infections. As a whole, a 3-foldecrease in the infection rate took place by the ad-inistration of antibiotics.

INFECTION RATES IN DIFFERENT LOCATIONS

All studies had their analysis primarily confined tohe dentate part of the mandible (ie, excluding theondylar region). In 1 study, the infection rate wasompared between various locations (Table 3). It ap-ears that infection was not found in the maxilla, theondylar region, or the zygoma, irrespective of admin-stration of antibiotics.8

INFECTION RATES RELATED TO ANTIBIOTICADMINISTRATION

There appears to be no difference in the reduction

S RELATED TO THE USE OR NOT OF ANTIBIOTICS

Test Group

Probability Level

Antibiotics

% No. x %

53 32 2 6 0.001

20

0.0640 2 540 4 10

22

0.00150 1 250 3 651 4 8

62 37 5 14 0.01

ac Surg 2006.

RATE

Group

iotics

ate of infection in the 4 studies.

pecms

swietttTnhip

jidc

sbs

acpl

tpddm

ett

R

1

1

1

1

1

1

1

1

1

1

2

2

2

2

2

2

ZMCM

D

AM

1668 ANTIBIOTICS FOR MAXILLOFACIAL FRACTURES

INFECTION RATE RELATED TO THE LENGTH OFANTIBIOTIC ADMINISTRATION

Three studies analyzed this parameter.13,14,16 It ap-ears that a “1-shot” or 1-day administration workedqually, or maybe even better (however, not signifi-antly), than a 7-day course. A similar finding has beenade for other approaches in oral and maxillofacial

urgery22 and in orthopedic surgery.3,23

The present study based on 4 quasi-randomizedtudies appeared to show a significant decrease inound infection (4-fold when antibiotics were admin-

stered). This finding can be compared with similarffects in the treatment of bone fractures of the ex-remities.24 This effect can be explained in the wayhat antibiotic treatment will reduce or eliminate bac-eria that have entered the wound before treatment.he first event seems to be the most obvious expla-ation, as prophylactic administration of antibioticsas not resulted in a significant reduction in wound

nfection after orthognathic surgery. In this situation,resurgical bacteria contamination is not present.An analysis of the bacteria flora infections related to

aw fractures is very sparse. In 1 study, a mixednfection with aerobic and anaerobic flora and a pre-ominance of staphylococcus aureus seems to indi-ate that specific antibiotics may be indicated.25

The great variety of antibiotics used in the citedtudies with varying specificity against the presumedacteria flora gives no significant clue concerning theelection of proper antibiotic.

The specific preference of wound infection to thengular region does support a dental origin (pulpanal or periodontal flora related to the molar maylay a role). This phenomenon will be further ana-

yzed in a subsequent study.In conclusion, a short-term antibiotic therapy (less

han 48 hours), possibly a 1-shot administration, ap-ears to be effective in protecting compound man-ibular fractures from infection, especially open re-uction. Because of the very low infection rate in

Table 3. COMPARISON OF POSTOPERATIVEINFECTION RATES ACCORDING TO FRACTURELOCATION

nInfection

(%)

ygoma 18 0 (0)axilla 6 0 (0)ondyle 23 0 (0)andible 79 23 (29)

ata from Chole and Yee 1987.8

ndreasen et al. Antibiotics for Maxillofacial Fractures. J Oralaxillofac Surg 2006.

axillary fractures, zygoma fractures, and the non-

xistence of infection complications in condylar frac-ures, antibiotic treatment in the latter types of frac-ures does not seem indicated.

eferences1. Haug RH, Assael LA: Infection in the maxillofacial trauma patient,

in Topazian RG, Goldberg MH, Hupp JR, eds. Oral and Maxillofa-cial Infections. Ed 4. Philadelphia, PA, Saunders, 2002, p 359

2. Chodak GW, Plaut ME: Use of systemic antibiotics for prophy-laxis in surgery. A critical review. Arch Surg 112:326, 1977

3. Stone HH, Haney BB, Kolb LD, et al: Prophylactic and preven-tive antibiotic therapy. Timing, duration and economics. AnnSurg 189:691, 1979

4. Guiglimo BJ, Hohn DC, Koo PJ, et al: Antibiotic prophylaxis insurgical procedures: A critical analysis of the literature. ArchSurg 118:943, 1983

5. Kaiser AB: Medical intelligence. Drug Therapy. Antimicrobialprophylaxis in surgery. N Engl J Med 315:1129, 1986

6. Paterson JA, Curdo VA, Stratigos GT: An examination of anti-biotic prophylaxis in oral and maxillofacial surgery. J Oral Surg28:753, 1970

7. Peterson L: Antibiotic prophylaxis against wound infection in oraland maxillofacial surgery. J Oral Maxillofac Surg 48:617, 1990

8. Chole RA, Yee J: Antibiotic prophylaxis for facial fractures.Arch Otolaryngol Head Neck Surg 113:1055, 1987

9. Andreasen JO, Jensen SS, Kofod T, et al: Open or closedrepositioning of jaw fractures, is there a difference in healingoutcome? A systematic review. Dent Traumatol In press

0. Jadad A: Randomized Controlled Trials: A User’s Guide. Lon-don, UK, BMJ Books, 1998

1. Shaw WC, Worthington HV, Harrison J, et al: Cochrane OralHealth Group, in The Cochrane Library, Issue 3, 2002. Oxford:Update Software

2. Zallen RD, Curry JT: A study of antibiotic usage in compoundmandibular fractures. J Oral Surg 33:431, 1975

3. Aderhold L, Jung H, Frenkel G: Untersuchungen über den werteiner Antibiotika Prophylaxe bei Kiefer-Gesichtsverletzungen –eine prospective Studie. Dtsch Zahnärztl Z 38:402, 1983

4. Gerlach KL, Pape H-D: Untersuchungen zur Antibiotikaprophy-laxe bei der operativen Behandlung von Unterkieferfrakturen.Dtsch Z Mund Kiefer Gesichts Chir 12:497, 1988

5. Heit JM, Stevens MR, Jeffords K: Comparison of ceftriaxonewith penicillin for antibiotic prophylaxis for compound man-dible fractures. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 83:423, 1997

6. Abubaker AO, Rollert MK: Postoperative antibiotic prophylaxisin mandibular fractures: A preliminary randomized, double-blind, and placebo-controlled clinical Study. J Oral MaxillofacSurg 59:1415, 2001

7. Sandusky WR: Use of prophylactic antibiotics in surgical pa-tients. Surg Clin North Am 60:83, 1980

8. Zallen RD, Strader RJ: The use of prophylactic antibiotics inextraoral procedures for mandibular prognathism. J Oral Surg29:178, 1971

9. Peterson LJ, Booth DF: Efficacy of antibiotic prophylaxis inintraoral orthognathic surgery. J Oral Surg 34:1088, 1976

0. Beckers H, Kühnle T, Dietrich H-G: Einfluss prophylaktischerAntibiose auf infektiöse Komplikationen nach Dysgnathieop-erationen. Forthschr Kiefer Gesicht 29:118, 1984

1. Zijderveld SA, Smeele LE, Kostense PJ, et al: Preoperative an-tibiotic prophylaxis in orthognathic surgery: A randomized,double-blind, and placebo-controlled clinical study. J Oral Max-illofac Surg 57:1403, 1999

2. Merten H-A, Halling F: Perioperativ Antibiotikaprofylaxe in derKiefer. Gesichtschirurgie 21(suppl 1):45, 1993

3. Keighley MRB: Use of antibiotics. Surgical infections. Br Med J17:1603, 1978

4. Ostermann PA, Henry SL, Seligson D: The role of local antibi-otic therapy in the management of compound fractures. ClinOrthop Rel Res 295:102, 1993

5. Pape H-D, Schaal K-P, Braun J: Erreger- und Resistenzspektrum

bei odontogenen Infektionen im Kiefergesichtsbereich.Fortschr Kiefer Gesicht 29:86, 1984